We investigated, to determine whether disruption of lipid rafts would influence the effect of three selected strains of Lactobacillus on TNF-alpha production by peripheral blood mononuclear cells. Two strains increased TNF-alpha production; and the third one reduced cytokine levels. Disruption of rafts changed the immunomodulatory effect of the three strains. This is the first report on a potential role of rafts in lactobacilli-cell interaction.